Diltiazem efficacy and CYP2D6 gene polymorphism in patients with atrial fibrillation with rapid ventricular response

Abstract

Background Diltiazem stands out as one of the front-line drugs administered in the emergency department to achieve acute rate control in patients suffering from atrial fibrillation with rapid Ventricular Response. One of the cytochrome enzymes involved in the metabolism of diltiazem is cytochrome P450 2D6 (CYP2D6). Interindividual differences can act on drug metabolism and thus drug efficacy due to the genetic polymorphism induced by the CYP2D6 enzyme. This study explores the association between the efficacy of diltiazem and the genetic polymorphism of CYP2D6 in patients with atrial fibrillation with rapid ventricular response. Results 87 out of 93 individuals with ventricular rate > 120 beats/min constituted the patient cohort. The patients were administered 0.25 mg/kg diltiazem intravenously. As a second dose, 0.35 mg/kg diltiazem was administered to patients who reportedly did not receive adequate drug efficacy. Heart rate control was considered to be achieved in patients whose heart rate fell below 110 beats/min and did not rise above 110 beats/min for 2 h. CYP2D6 *2, *3, *4 and *10 represent allele variants and *1 represents wild type (wt) allele. Achieving rate control after one or two doses of diltiazem in normal allele (wt/wt) carriers proved significantly higher than wt/*2, wt/*4 and wt/*10 heterozygous variant carriers. No significant difference was noted in wt/*3 heterozygous variant carriers. Conclusion The presence of *2, *4 and *10 alleles was observed to significantly compromise the drug efficacy. *3 allele was found to bear no relation to the effect of diltiazem on achieving rate control.